Role of Complement Cascade in Abdominal Aortic Aneurysms
| Autor: | Larry A. Donoso, James R. Elmore, Glenn S. Gerhard, David J. Carey, William D. Bowen, Gerard Tromp, Kimberly Derr, Robert P. Garvin, Nikos Tapinos, Charles M. Schworer, Amy M. Boddy, Helena Kuivaniemi, Irene Hinterseher, David P. Franklin, Tamara R. Vrabec, John H Lillvis, Robert Erdman, Zoran Gatalica, Alicia Golden, John L. Gray |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Chromatin Immunoprecipitation Biology Article STAT5 Transcription Factor Humans RNA Messenger Promoter Regions Genetic Complement Activation Transcription factor Aged Oligonucleotide Array Sequence Analysis Aged 80 and over Genetics Regulation of gene expression Binding Sites Polymorphism Genetic Complement component 2 Gene Expression Profiling Tumor Suppressor Proteins Promoter Complement System Proteins Complement C2 Middle Aged Immunohistochemistry Cell biology Complement system DNA binding site Gene expression profiling Gene Expression Regulation Case-Control Studies Female Cardiology and Cardiovascular Medicine Chromatin immunoprecipitation Aortic Aneurysm Abdominal Genome-Wide Association Study |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 31:1653-1660 |
| ISSN: | 1524-4636 1079-5642 |
| Popis: | Objective— The goal of this study was to investigate the role of complement cascade genes in the pathobiology of human abdominal aortic aneurysms (AAAs). Methods and Results— Results of a genome-wide microarray expression profiling revealed 3274 differentially expressed genes between aneurysmal and control aortic tissue. Interestingly, 13 genes in the complement cascade were significantly differentially expressed between AAA and the controls. In silico analysis of the promoters of the 13 complement cascade genes showed enrichment for transcription factor binding sites for signal transducer and activator of transcription (STAT)5A. Chromatin-immunoprecipitation experiments demonstrated binding of transcription factor STAT5A to the promoters of the majority of the complement cascade genes. Immunohistochemical analysis showed strong staining for C2 in AAA tissues. Conclusion— These results provide strong evidence that the complement cascade plays a role in human AAA. Based on our microarray studies, the pathway is activated in AAA, particularly via the lectin and classical pathways. The overrepresented binding sites of transcription factor STAT5A in the complement cascade gene promoters suggest a role for STAT5A in the coordinated regulation of complement cascade gene expression. |
| Databáze: | OpenAIRE |
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